Gluten and gluten-related polypeptides are found in many cereal grains, including wheat, rye and barley. For individuals with gluten-related disorders such as celiac disease and gluten sensitivity, consumption of gluten-containing foods can have severe and long-lasting health consequences. Celiac disease is an autoimmune disorder of the small intestine that is triggered by gluten consumption in genetically predisposed people. Certain fragments of gluten (“gliadins”) stimulate an immune response that permanently damages the small intestine and prevents nutrient absorption. Celiac disease can present with a wide spectrum of symptoms. The most common ones include chronic diarrhea, abdominal distention, weight loss, and failure to thrive (in children). Celiac disease can also be associated with iron deficiency anemia, osteoporosis, short stature, arthritis, infertility, peripheral neuropathy and liver failure. Celiac disease patients are also at increased risk for certain kinds of cancers, such as small bowel carcinomas and non-Hodgkin lymphoma. The incidence of celiac disease in populations of European descent is estimated to be between 0.5 and 1.5%. The incidence is increasing both in the U.S. and Europe, as well as in Asia, in part due to the adoption of westernized dietary patterns. Celiac disease is typically diagnosed in infancy or childhood, although the numbers of diagnoses made in adulthood is also on the rise. There is presently no cure for celiac disease and the standard treatment is a life-long restriction to a gluten-free diet.
Gluten sensitivity is less well-characterized than celiac disease. It presents with many of the same symptoms, but does not include the damage to the small intestine. The diagnosis tends to be made on exclusion criteria and improvement of symptoms once the patient is put on a gluten-free diet.
Adherence to a gluten-free diet requires strict avoidance of wheat, rye and barley products. This can be challenging given the often insufficient labeling information about the gluten content of foods; the opportunity for contamination during food processing and preparation, especially for those food prepared in outside the home; the financial burden of gluten-free products, and the willpower required for strict adherence. Compliance can also be affected by access to education and counseling, family and social support, and psychological factors. Moreover, strict adherence to a gluten-free diet can result in micronutrient deficiencies. Such deficiencies, particularly in the B vitamins (vitamin B6, vitamin B12 and folic acid) and certain trace elements, e.g., iron, zinc and copper, can result in potentially significant health issues, particularly in children. There is a continuing need for therapeutic agents for the treatment of gluten-related disorders.